The proposed research will attempt to analyze, from a biochemical approach, the mechanisms by which gene activity can control the formation of connections between nerve cells. Two of these mechanisms, directed growth and intercellular recognition, have been demonstrated to occur in the cockroach, periplaneta americana, during the regeneration of motor neurons whose axons have been disrupted. These mechanisms generate sufficient specificity so that when regeneration is complete, individual identified motor neurons are observed to make functional connections only with the leg muscles to which they were originally attached. Attempts will be made to identify and characterize the cell surface macromolecules, in the muscles and the motor neurons, whose interactions are presumably responsible for the specific intercellular recognition process. The development of an organ culture system in which axons of the motor neurons grow from the ganglion and specifically reinnervate the muscles will enable a study of the mechanism of the directed growth. Although regeneration has been used as a model for the events occurring during embryonic development, it is necessary to investigate whether the same mechanisms of genetic control are active during both. This will be done through a histological study of the growing embryonic motor neurons as well as through a study of the behavior of the embryonic tissues in vitro.